MicroRNA regulation and therapeutic targeting of survivin in cancer.
MicroRNA regulation and therapeutic targeting of survivin in cancer.
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DOI：
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发表时间：
2015
影响因子：
5.3
通讯作者：
Jingcao Huang;H. Lyu;Jianxiang Wang;Bolin Liu
中科院分区：
文献类型：
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作者：
Jingcao Huang;H. Lyu;Jianxiang Wang;Bolin Liu
Survivin 是 IAP（凋亡抑制剂）家族中最小的成员，是一种双重功能蛋白，充当关键的凋亡抑制剂和关键的细胞周期调节剂。生存素通常在发育过程中的胚胎组织中表达，并且在大多数终末分化组织中检测不到。大量研究表明，生存素在几乎所有类型的人类恶性肿瘤中选择性上调，其过度表达与不良预后、肿瘤复发和治疗耐药呈正相关。生存素在肿瘤和正常组织中的这种差异表达引起了人们对开发针对癌症治疗的生存素靶向疗法的极大兴趣。尽管如此，控制恶性肿瘤细胞中生存素表达的分子机制尚未完全了解。虽然受体酪氨酸激酶 (RTK) 和下游信号传导（例如 PI-3K/Akt、MEK/MAPK、mTOR 和 STAT 通路）的异常激活经常被证明会上调生存素，但最近的数据表明，一类非编码 RNA、microRNA (miRNA) 在人类癌症中的生存素失调中也发挥着重要作用。在此，我们重点关注与survivin mRNA 3'-UTR结合的特定miRNA调控survivin表达，并总结survivin靶向治疗临床试验的最新进展以及survivin靶向miRNA在癌症中的治疗潜力。
Survivin, the smallest member of IAP (inhibitor of apoptosis) family, is a dual functional protein acting as a critical apoptosis inhibitor and key cell cycle regulator. Survivin is usually expressed in embryonic tissues during development and undetectable in most terminally differentiated tissues. Numerous studies demonstrate that survivin is selectively upregulated in almost all types of human malignancies and its overexpression positively correlates with poor prognosis, tumor recurrence, and therapeutic resistance. This differential expression of survivin in tumors and normal tissues draws a great interest to develop survivin-targeted therapy for cancer treatment. Nonetheless, the molecular mechanisms controlling survivin expression in malignant tumor cells have not been fully understood. While aberrant activation of receptor tyrosine kinases (RTKs) and the downstream signaling, such as PI-3K/Akt, MEK/MAPK, mTOR, and STAT pathways, have frequently been shown to upregulate survivin, recent data suggest that a class of noncoding RNAs, microRNAs (miRNAs) also play an important role in survivin dysregulation in human cancers. Here, we focus on survivin expression-regulated by specific miRNAs binding to the 3'-UTR of survivin mRNA, and summarize the latest advances on survivin-targeted therapy in clinical trials and the therapeutic potential of survivin-targeting miRNAs in cancer.